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The Effect of Terazosin on Women with Voiding DysfunctionNg PY, Tan GI, J Ravi

Urogynaecology Unit, Department of Obstetrics and Gynaecology, Hospital Kuala Lumpur, Malaysia

Objectives

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inINTRODUCTION Female voiding dysfunction encompasses those with difficulty emptying the bladder whether due to an inability to contract the detrusor effectively, bladder outflow obstruction, loss of detrusor-sphincter coordination, or a combination of these. The prevalence of voiding phase dysfunction in women has been reported to be 2-25.5% among women referred for the evaluation of lower urinary tract symptoms (1). Moreover, recent studies show that a1-AR antagonists effectively improve symptoms and voiding parameters in women with functional bladder outlet obstruction or detrusor underactivity (2-4). Because a1-ARs appear to play roles in lower urinary tract function at multiple sites and levels, including the bladder neck and external urethral sphincter, and because these non-prostate effects should be gender-independent, it seems logical that a 1-AR antagonists could be used in women with voiding dysfunction (5-8). However, little clinical evidence is available to indicate that a1-AR antagonists are effective in female patients with voiding dysfunction. In this study, we evaluated the potential therapeutic effects of a1-AR antagonists using terazosin.

OBJECTIVE

We assessed the effect of terazosin (Hytrin®) on women with voiding dysfunction.

Methods

This is a cross sectional study done in Urogynaecology clinic in Hospital Kuala Lumpur from 1st July 2011 till 28th Feb 2012. All female patients who had suffered from symptoms of voiding dysfunctions for at least 3 months were enrolled in this study.

Inclusion criteria:- Age ≥18 yr,-Maximum flow rate (Qmax) ≤12 mL/sec-Postvoid residuals (PVR) ≥120 mL.

Exclusion criteria-Patients with possible neurogenic voiding dysfunction-Anatomical bladder outlet obstruction (e.g., urethral stricture, bladderneck contracture, bladder calculi, bladder tumor, severe pelvic organ prolapse, urethral diverticulum,etc.) -Patients with active urinary tract infection (UTI), history of recurrent UTIs -Suspected interstitial cystitis, -On medications ( alpha-1 blockers and/or anticholinergics within 7 days before the enrolment, estrogen replacement started within 2 months)-Had electrostimulation and/or bladder training within the 14 days proceeding the enrollment

Terazosin was initiated at 1 mg daily and gradually increased to the maintenance dose of 2= 4 mg daily during 2 weeks and maintained for 8 weeks. Medications, such as cholinergic drugs(e.g. bethanechol chloride), and other a-AR antagonists, were not permitted throughout the 8 week trial period. All patients underwent an urologynaecologicalical evaluation that included medical history taking, pelvic examination, a neurourologic examination, urinalysis, urine culture. Urodynamic studies were performed accordingly.

Treatment outcomes were evaluated using PVR,number of micturitions (including 24 hr-, diurnal and nocturnal).

Statistical analysis done using SPSS version 20. A P value of less than 0.05 is considered significant

Results

A total of 10 patients who met the criteria were enrolled in the study. The demographic data were as follows:

The symptoms were as follows:

Changes following treatment

Reduction (%) in PVR

Conclusions

References

Our results show that the alpha blocker ie Terazosin has a beneficial effect on PVR, diurnal and nocturnal frequencies in women with non-neurogenic voiding dysfunction.. Terazosin had a significant symptomatic and urodynamic effect in 69% of our patients. These results suggest that terazosin may be an effective treatment option in women with voiding dysfunction due to functional bladder outlet obstruction. This study is similar to Kessler et al (9) who reported a 67% improvement rate.An animal study showed that the densities and affinities of a1-AR in male and female urethras are similar (6, 8). Nasu et al. (7) showed no significant differences between male and female urethras in terms of the cross-sectional distributions of AR subtype mRNAs which control the urethral tone.Terazosin demonstrated effectiveness in female patients with voiding dysfunction .A majority of patients showed subjective and objective improvements and were satisfied with treatment.To further determine the efficacy of a1-AR antagonists in women with voiding dysfunction a long-term, randomized, controlled study is required to compare the efficacy of a1-AR antagonists versus placebotreatment.Our findings suggest that a1-AR antagonists offer aninitial treatment option for female with non-neurogenic voiding dysfunction.

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1.Groutz A, Blaivas JG. Non-neurogenic female voiding dysfunction. Curr Opin Urol 2002; 12: 311-62. Kessler TM, Studer UE, Burkhard FC. The effect of terazosin on functional bladder outlet obstruction in women: a pilot study. J Urol 2006;176: 1487-92.3. Pischedda A, Pirozzi Farina F, Madonia M, Cimino S, Morgia G. Use of alpha1-blockers in female functional bladder neck obstruction. Urol Int 2005; 74: 256-61.4. Yamanishi T, Yasuda K, Kamai T, Tsujii T, Sakakibara R, Uchiyama T, Yoshida K. Combination of a cholinergic drug and an alphablockeris more effective than monotherapy for the treatment of voiding difficulty in patients with underactive detrusor. Int J Urol 2004;5.. Andersson KE, Lepor H, Wyllie MG. Prostatic alpha 1-adrenoceptors and uroselectivity. Prostate 1997; 30: 202-15.6. Morita T, Latifpour J, O'Hollaren B, Wheeler MA, Weiss RM. Sex differences in function and distribution of alpha 1- and alpha 2-adrenoceptors in rabbit urethra. Am J Physiol 1987; 252: F1124-8.7. Nasu K, Moriyama N, Fukasawa R, Tsujimoto G, Tanaka T, Yano J, Kawabe K. Quantification and distribution of alpha1-adrenoceptor subtype mRNAs in human proximal urethra. Br J Pharmacol 1998; 123: 1289-93.8. Yablonsky F, Riffaud JP, Lacolle JY, Dausse JP. Alpha 1- and alpha 2-adrenoceptors in the smooth muscle of male and female rabbit urethra. Eur J Pharmacol 1986; 121: 1-8.9. KesslerTM, Studer UE, Burkhard FC, The effect of terazosin on functional bladder outlet obstruction in women: a pilot study. J Urol 2006 Oct;176(4 Pt 1):1487-92.

Demographic factors Range

Age (yrs) 62.9 ( 48-75)

Parity (n) 4 (1-7)

Race - n (%)- Malay -Chinese-Indian

-3 (30%)7 ( 70%)

Menopause – n (%)-Yes- No

9 (90%)1 (10%)

Symptoms N (%)

Increased frequency 9 (90)

Nocturia 10 (100)

Urgency 9 (90)

Poor stream 8 (80)

Incomplete emptying 8 (80)

Parameters

Pre treatment

Post treatment

P value

Daytime frequency (n)

10.6+ 2.6 7.8 + 2.4 0,02

Nocturia (n) 2.9 + 1.3 1.7+ 1.2 0.04

Post void residual urine (mls)

179.4 + 56.0

89. 3 + 53.9

0.02

Average in reduction (%)

51.9 (10- 72.8)

Number of patients with more than 50%- n (%)

6 (60)

Average reduction more than patients more than 50% improvement - (%)

69.1 (58.5 to 72.8)